The Pharmaceutical Journal
Vol 270 No 7237 p261
22 February 2003

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New England Journal of Medicineabstract (more)

ACE inhibitors superior to diuretics, trial suggests

Treating high blood pressure with angiotensin-converting-enzyme (ACE) inhibitors may result in fewer cardiovascular events among elderly people than treatment with diuretics, new data suggest. Furthermore, the benefit may be particularly evident among men.

Researchers compared the effects of enalapril with those of hydrochlorothiazide in 6,083 elderly hypertensive patients. Although these drugs were the recommended therapies, the choice of agent and dose was made by the patient's general practitioner. To achieve target blood pressure, addition of beta-blockers, calcium channel blockers and alpha-blockers was allowed for all patients. Subjects were followed for an average of 4.1 years.

The researchers report that, by the end of the study, blood pressure reductions were similar for both treatment groups. However, cardiovascular events or deaths occurred less frequently among patients assigned to ACE inhibitor therapy than among those assigned to a diuretic (hazard ratio 0.89, 95 per cent confidence interval, 0.79 to 1.00, P=0.05). Among male patients, the hazard ratio was 0.83 (0.71 to 0.97, P=0.02), and among female patients it was 1.00 (0.83 to 1.21, P=0.98).

Rates of non-fatal cardiovascular events and myocardial infarctions decreased with ACE inhibitor treatment, whereas a similar number of strokes occurred in each group. The researchers comment that because men have a higher cardiovascular risk than women, "ACE-inhibitor treatment may be of particular advantage . . . because of factors that influence the atherosclerotic process, such as stability of plaque and endothelial function" (New England Journal of Medicine 2003;348:583).

In an accompanying editorial (ibid p639), Dr Edward Frohlich, of the Ochsner Clinic Foundation in New Orleans, discusses why the results of the study seem to contradict those of another major trial — the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) — which found that diuretics were more effective than ACE inhibitors for blood-pressure control.

He suggests that health care providers should assume more direct control of the interpretation of studies, since trials compare different therapies and use different definitions of clinical outcomes.

He concludes: "We must remember that trials describe population averages ... whereas physicians must focus on the individual patient's clinical responses."